Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization

Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associat...

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Main Authors:	Vale-Silva, Luis A., Moeckli, Beat, Torelli, Riccardo, Posteraro, Brunella, Sanguinetti, Maurizio, Sanglard, Dominique
Format:	Online
Language:	English
Published:	American Society for Microbiology 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863579/

id	pubmed-4863579
recordtype	oai_dc
spelling	pubmed-48635792016-06-14 Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization Vale-Silva, Luis A. Moeckli, Beat Torelli, Riccardo Posteraro, Brunella Sanguinetti, Maurizio Sanglard, Dominique Research Article Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients. American Society for Microbiology 2016-03-02 /pmc/articles/PMC4863579/ /pubmed/27303714 http://dx.doi.org/10.1128/mSphere.00065-15 Text en Copyright © 2016 Vale-Silva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Vale-Silva, Luis A. Moeckli, Beat Torelli, Riccardo Posteraro, Brunella Sanguinetti, Maurizio Sanglard, Dominique
spellingShingle	Vale-Silva, Luis A. Moeckli, Beat Torelli, Riccardo Posteraro, Brunella Sanguinetti, Maurizio Sanglard, Dominique Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
author_facet	Vale-Silva, Luis A. Moeckli, Beat Torelli, Riccardo Posteraro, Brunella Sanguinetti, Maurizio Sanglard, Dominique
author_sort	Vale-Silva, Luis A.
title	Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
title_short	Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
title_full	Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
title_fullStr	Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
title_full_unstemmed	Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization
title_sort	upregulation of the adhesin gene epa1 mediated by pdr1 in candida glabrata leads to enhanced host colonization
description	Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients.
publisher	American Society for Microbiology
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863579/
_version_	1613578012530311168

Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization

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